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A disrupted biological clock: a risk factor for anxiety disorders

In mammals, light is essential in order for the body to function properly. This response to light is controlled in our bodies by a biological clock. Like well-oiled clockwork, the central clock located in a small structure of the brain known as the hypothalamus in turn synchronises numerous secondary clocks present in other areas of the brain, and in some peripheral organs. These clocks control the expression of many genes that allow the body to adapt to the environment on a daily basis.

A disruption in the molecular components of the biological clock is often associated with psychiatric disorders, but the question of causality has remained unanswered until now.

To tackle this question, a team of Inserm researchers led by Emmanuel Valjent (ATIP/Avenir Team, Inserm Unit 661, Institute for Functional Genomics, Montpellier), evaluated a range of behaviours associated with psychiatric illnesses, using mice in which two essential genes for the circadian clock (cryptochrome 1 and cryptochrome 2) had been inactivated.

Their work demonstrated causal relationships between the disruption of genes encoding the cryptochrome 1 and 2 proteins (Cry1 and 2) and anxiety-related behaviours.

Indeed, mice deficient in Cry1 and 2 proteins, in which the clock is disrupted, showed characteristic behavioural changes that included an abnormally high level of anxiety.

This is reflected in rodents by an increased aversion to open spaces. Interestingly, mice deficient in either of the Cry1 or Cry2 proteins, in which the biological clock is only slightly altered, showed the same behavioural changes.

These results clearly indicate that, apart from their critical roles in the regulation of the molecular clock, these proteins are directly involved in controlling the emotional state. This study, published in the journal Frontiers in Behavioural Neuroscience, enables a better understanding of the complex relationship between the biological clock and behaviours associated with psychiatric illnesses such as anxiety.

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Researcher Contact

Emmanuel Valjent, PhD
CR1 Inserm – Group Leader “ATIP-Avenir Team”
Institut de Génomique Fonctionnelle
Department of Neurobiology
Inserm U661, UMR 5203 CNRS, University Montpellier I & II

Tel : 04 34 35 92 22


Cognitive dysfunction, elevated anxiety, and reduced cocaine response in circadian clock-deficient cryptochrome knockout mice
Dimitri De Bundel1,2,3*†, Giuseppe Gangarossa1,2,3†, Anne Biever1,2,3, Xavier Bonnefont1,2,3 and Emmanuel Valjent1,2,3*

1CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France
2INSERM, U661, Montpellier, France
3Universités de Montpellier 1 and 2, UMR-5203, Montpellier, France

Frontiers in behavorial Neuroscience